Modification of neutrophil function by plasma of rheumatoid arthritis patients treated with infliximab

CER2720
2006 Vol.24, N°1
PI 0038, PF 0044
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PMID: 16539817 [PubMed]

Abstract

OBJECTIVES:
To examine whether the release of superoxide anions from neutrophils of healthy donors was affected when incubated with plasma from infliximab-treated rheumatoid arthritis (RA) patients.
METHODS:
Fifteen consecutive seropositive RA patients were treated with 3mg/kg infliximab on weeks 0, 2, 6, and 14. Disease activity was assessed by DAS28 score and by IL-6 level. Neutrophils from healthy donors were incubated with plasma drawn before each infliximab treatment. PMA-stimulated superoxide release was measured by the ferricytochrome C reduction method.
RESULTS:
53% of the patients had a favorable clinical response. IL-6 levels showed a significant decline at week two, with a gradual increase thereafter. Treatment with infliximab did not change the superoxide production. However, when the group was divided retrospectively to responders (&Dgr;DAS28 > -1.2) and non-responders (&Dgr;DAS28 < -1.2), two different patterns were seen, although the pre-treatment levels were similar: Among the responders IL-6 remained low at its 2 weeks level till week 14, while in the non responders IL-6 increased 3 times (P < 0.03) from week 2 to 14. The responders showed mild, but continuous, reduction of superoxide release, while in the non-responders it increased significantly from week 2 on.
CONCLUSIONS:
The reduction in IL-6 in RA sera following anti-TNFα therapy has little influence on the capacity of these sera to stimulate healthy neutrophils to produce superoxide, suggesting the existence of non-TNFα non-IL-6 dependent neutrophil-stimulating mediators in RA sera. The increasing level of IL-6 among the non-responders after initial dramatic decline might represent an escape phenomenon, possibly caused by alternative mediator(s). Clinically, this IL-6 `escape` might be used as a tool for early identification of responders from non-responders.